The overall goal of this project is to develop a self-help smoking cessation with an integrated weight control component. The product, LifeSign for weight control (LS-WC), will provide a simple to follow behavior change program that modifies smoking rate and eating and exercise habits simultaneously. The LS-WC program, composed of a hand- held computer and a written program guide, will be targeted to consumers, primarily women, for whom concern over weight gain is a significant impediment to successful smoking cessation. The product will combine, integrate, and extend features from two programs developed by PICS: the LifeSign Smoking Cessation Program and the DietMate Weight Control Program. During Phase I, we will develop a fully-functional prototype of the product and assess feasibility through a small-scale clinical study examining smoking cessation and weight gain among 90 smokers assigned to either gradual reduction plus weight control or gradual reduction alone. During Phase II, we will modify the product, based on results and feedback obtained during Phase I, and conduct a larger study with appropriate controls and follow-up to further evaluate the effectiveness and desirability of the product. PROPOSED COMMERCIAL APPLICATION: Despite significant progress made during the past 30 years, cigarette smoking remains a monumental public health problem. Substantial evidence suggests that fear of weight gain deters many smokers from quitting. A program that effectively integrates smoking cessation and weight control may prove to be commercially viable and have a positive public health impact. GRANT=R43CA80515 Current gene therapy vectors employ animal viruses or condensed DNA/protein complexes to deliver DNA. The use of animal viruses has been limited because of tropism for normal cells, associated toxicity, the cost of large-scale production, and the difficulty of genetically altering a complicated virus. Nonviral systems offer an alternative but are difficult to produce with the same homogeneity of a virus. We aim to improve current gene therapy methods by developing an alternative gene delivery vehicle, the bacteriophage, that is simple and economical to produce and lacks native tropism for mammalian cells. By demonstrating that genetically targeted phage can transduce mammalian cells we propose here to add other accessory peptides and DNA elements involved in trafficking, phage replication and integration to the phage vector with the goal of enhancing the transduction efficiency such that the targeted phage will the phage vector with the goal of enhancing the transduction efficiency such that the targeted phage will be useful for gene therapy. The long-term goal of this proposal is, therefore, to develop a safe, economical, and effective alternative to existing gene therapy vectors for therapeutic gene delivery to treat cancer and other diseases. PROPOSED COMMERCIAL APPLICATION: We propose to develop bacteriophage as an improved alternative to existing gene delivery methods. The commercial applications include reduced production costs and improved gene therapy of cancer and gene replacement therapy. Our strategy will be to genetically alter the phage vector to confer efficient mammalian cell tropism. The vector will be targeted to specific receptor bearing cells using a ligand that is displayed on the tip of the phage particle as a genetic fusion to a phage coat protein. Our goal is to establish the use of phage as a safe and effective alternative vehicle for therapeutic gene delivery.